The aim of this investigation is to advance the understanding of the proliferative behavior of normal and neoplastic hematopoietic cells. The effort will be largely theoretical, and will seek to develop improved mathematical models of the normal hematopoietic cell production system and the growth and development of the leukemic neoplasm. It is hoped that such cellular kinetic models will lead to a clearer comprehension of the nature of the fundamental abnormalities in the hematopoietic tumors, and to more effective chemotherapeutic drug treatment regimens. In close formal collaboration with Dr. B. D. Clarkson, it is intended to study particularly patients with acute leukemia during and following chemotherapy, to determine the effects of the interaction between drugs and the hematopoietic system, with a view to providing a rational basis for drug scheduling. A mathematical model for the evaluation of data from flow microfluorometry will be formulated, so as to aid the interpretation of changing FMF patterns in cell populations subject to perturbations, such as occur during chemotherapy. The cloning capacity in semi-solid media of both normal leukocyte precursors and of leukemic cells will be studied, so as to enhance the understanding of the hematopoietic production system leading from stem cells to mature blood cells, and the influence of regulatory factors.